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神经发育障碍和不同类型癌症中的赖氨酸乙酰转移酶6复合物

Lysine Acetyltransferase 6 Complexes in Neurodevelopmental Disorders and Different Types of Cancer.

作者信息

Mousavi Negar, Yang Xiang-Jiao

机构信息

Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.

Department of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Results Probl Cell Differ. 2025;75:391-410. doi: 10.1007/978-3-031-91459-1_14.

DOI:10.1007/978-3-031-91459-1_14
PMID:40593218
Abstract

Lysine acetylation is a critical post-translational modification that regulates gene expression and cellular functions. The MYST family lysine acetyltransferases KAT6A (also known as MOZ and MYST3) and KAT6B (a.k.a. MORF and MYST4), in complex with the multivalent epigenetic regulator BRPF1, play key roles in hematopoietic and neural development. Dysregulation of these complexes is implicated in neurodevelopmental disorders, such as Genitopatellar and Say-Barber-Biesecker-Young-Simpson syndromes, as well as in various cancers, including leukemia and medulloblastoma. The evolutionary conservation of these complexes in Drosophila melanogaster and Caenorhabditis elegans underscores their fundamental biological significance. Understanding the structural and functional mechanisms of KAT6-BRPF1 complexes provides insight into their pathological roles and therapeutic potential.

摘要

赖氨酸乙酰化是一种关键的翻译后修饰,可调节基因表达和细胞功能。MYST家族赖氨酸乙酰转移酶KAT6A(也称为MOZ和MYST3)和KAT6B(又名MORF和MYST4)与多价表观遗传调节剂BRPF1形成复合物,在造血和神经发育中起关键作用。这些复合物的失调与神经发育障碍有关,如生殖器髌骨综合征和Say-Barber-Biesecker-Young-Simpson综合征,以及各种癌症,包括白血病和髓母细胞瘤。这些复合物在黑腹果蝇和秀丽隐杆线虫中的进化保守性凸显了它们的基本生物学意义。了解KAT6-BRPF1复合物的结构和功能机制有助于深入了解它们的病理作用和治疗潜力。

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本文引用的文献

1
Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.多功能酰基转移酶 HBO1:细胞功能的关键调节因子。
Cell Mol Biol Lett. 2024 Nov 14;29(1):141. doi: 10.1186/s11658-024-00661-y.
2
ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.ERα 状态的浸润性导管乳腺癌是赖氨酸去乙酰化酶 KAT6A 和 KAT6B 之间的调控相互作用的结果。
Sci Rep. 2024 Nov 6;14(1):26935. doi: 10.1038/s41598-024-78432-0.
3
Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers.
必需基因筛选确定含溴结构域蛋白BRPF1是内分泌治疗耐药乳腺癌的一个新的可作用靶点。
Mol Cancer. 2024 Aug 7;23(1):160. doi: 10.1186/s12943-024-02071-2.
4
A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes.MOZ-TIF2 白血病小鼠模型表现出 KAT6 依赖性 H3K23 丙酰化和一组活跃发育基因的过表达。
Proc Natl Acad Sci U S A. 2024 Jun 25;121(26):e2405905121. doi: 10.1073/pnas.2405905121. Epub 2024 Jun 18.
5
The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function.组蛋白乙酰转移酶 KAT6B 对于造血干细胞的发育和功能是必需的。
Stem Cell Reports. 2024 Apr 9;19(4):469-485. doi: 10.1016/j.stemcr.2024.02.005. Epub 2024 Mar 21.
6
Exploiting epigenetic targets to overcome taxane resistance in prostate cancer.利用表观遗传靶点克服前列腺癌中的紫杉烷耐药性。
Cell Death Dis. 2024 Feb 12;15(2):132. doi: 10.1038/s41419-024-06422-1.
7
Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder.超越“言语迟缓”:扩展 BRPF1 相关障碍的表型。
Eur J Med Genet. 2024 Apr;68:104923. doi: 10.1016/j.ejmg.2024.104923. Epub 2024 Feb 10.
8
De novo KAT6B mutation causes Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome in an Iranian boy: a case report.伊朗男孩患 Say-Barber-Biesecker-Young-Simpson 变异型 Ohdo 综合征,其 KAT6B 基因存在新生突变:病例报告。
J Med Case Rep. 2024 Jan 5;18(1):4. doi: 10.1186/s13256-023-04237-w.
9
Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory.前脑兴奋性神经元特异性缺失Brpf1会减弱兴奋性突触传递,并损害空间记忆和恐惧记忆。
Neural Regen Res. 2024 May;19(5):1133-1141. doi: 10.4103/1673-5374.385307.
10
Expression profiles and functional prediction of histone acetyltransferases of the MYST family in kidney renal clear cell carcinoma.MYST 家族组蛋白乙酰转移酶在肾透明细胞癌中的表达谱及功能预测。
BMC Cancer. 2023 Jun 26;23(1):586. doi: 10.1186/s12885-023-11076-x.